HIV-1 binds dynein directly to hijack microtubule transport machinery
HIV-1 uses the microtubule cytoskeleton to reach the host cell nucleus during replication, yet the molecular basis for microtubule-dependent HIV-1 motility is poorly understood. Using in vitro reconstitution biochemistry and single-molecule imaging, we found that HIV-1 binds to the retrograde microtubule-associated motor, dynein, directly and not via a cargo adaptor, as has been previously suggested. The HIV-1 capsid lattice binds to accessory chains on dynein's tail domain. Further, we demonstrate that multiple dynein motors tethered to rigid cargoes, such as HIV-1 capsids, display reduced motility, distinct from the behavior of multiple motors on membranous cargoes. Our results provide an updated model of HIV-1 trafficking wherein HIV-1 binds to dynein directly to "hijack" the dynein transport machinery for microtubule motility.
Authors
- Sevnur Kömürlü Keceli (ORCID: https://orcid.org/0009-0002-0358-4753)
- Tobias W. Giessen (ORCID: https://orcid.org/0000-0001-6328-2031)
- Wang Peng (ORCID: https://orcid.org/0000-0002-7304-1482)
- Michael A. Cianfrocco (ORCID: https://orcid.org/0000-0002-2067-4999)
- Drew Lichon (ORCID: https://orcid.org/0009-0009-7567-2884)
- Michael P. Andreas (ORCID: https://orcid.org/0000-0001-8871-3053)
- Till Böcking (ORCID: https://orcid.org/0000-0003-1165-3122)
- Somayesadat Badieyan (ORCID: https://orcid.org/0000-0002-4728-013X)
- Christopher Aiken (ORCID: https://orcid.org/0000-0002-2476-4078)
- Morgan E. DeSantis (ORCID: https://orcid.org/0000-0002-4096-8548)
- John P. Gillies (ORCID: https://orcid.org/0000-0001-9659-5579)
- Edward M. Campbell (ORCID: https://orcid.org/0000-0001-5665-9195)
- Jiong Shi
Institutions
- Loyola University Chicago (US)
- University of Michigan (US)
- UNSW Sydney (AU)
- EMBL Australia (AU)
- Michigan Medicine (US)
- ARC Centre of Excellence in Advanced Molecular Imaging (AU)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-06-18
- DOI
- https://doi.org/10.1126/sciadv.adn6796
- Citations
- 2
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 2.07